论文标题

一项涉及至关重要的生物标记和最佳药物方案的综合且详细的内部建模研究,用于LEPRA I型反应:确定性方法

A Comprehensive and Detailed Within-Host Modeling Study involving crucial Bio markers and Optimal Drug regimen for Lepra Type-I Reaction : A Deterministic Approach

论文作者

Nayak, Dinesh, Chhetri, Bishal, Vamsi, D. K. K., Muthusamy, Swapna, Bhagat, Vijay M.

论文摘要

麻风病(汉森病)是一种由麻风分枝杆菌(M. Leprae)引起的感染性,被忽视的热带疾病。每年在全球发现大约有2,02,189例新病例。在2017年,由于麻风病,有超过500万人被残疾,并且每年在全球范围内增加近50000例新案件。在麻风病中,麻风反应是导致残疾的神经损伤的主要原因。通过研究生物标志物对LEPRA反应的早期检测在预防随后的残疾中具有重要作用。据我们所知,在涉及关键生物标志物以及可能用于麻风病和麻风反应的最佳药物方案的细胞内建模的文献似乎非常有限。在这项研究中,我们提出并分析了一个三维数学模型,以捕获易感的Schwann细胞,感染的Schwann细胞和基于麻风病的发病机理的细菌负荷的动力学。我们估计了来自各种临床论文的参数,以使模型更加实用。通过PRCC方法评估了几个参数的敏感性,以找出最具影响力的参数,并使用SRCC方法研究了两个最具影响力参数的组合。使用SOBOL指数评估了其他剩余参数的灵敏度。然后,考虑到多种药物治疗(MDT)作为控制变量,我们已经构造并研究了一个最佳控制问题。我们进一步研究了这个最佳控制问题以及MDT和类固醇干预措施。这项新颖而全面的研究的发现将有助于参与消除和消除麻风病过程的临床医生和公共卫生研究人员。

Leprosy (Hansen's disease) is an infectious, neglected tropical disease caused by the Mycobacterium Leprae (M. Leprae). Each year there are approximately 2,02,189 new cases are detected globally. In the year 2017 more than half million people were disabled due to leprosy and almost 50000 new cases are added every year world wide. In leprosy, lepra reactions are the major cause for nerve damage leading to disability. Early detection of lepra reactions through study of biomarkers have important role in prevention of subsequent disabilities. To our knowledge there seems to be very limited literature available on within-host modeling at cellular level involving the crucial biomarkers and the possible optimal drug regimen for leprosy disease and lepra reactions. Motivated by these observations, in this study, we have proposed and analyzed a three dimensional mathematical model to capture the dynamics of susceptible schwann cells, infected schwann cells and the bacterial load based on the pathogenesis of leprosy. We estimated the parameters from various clinical papers to make the model more practical. The sensitivity of couple of parameters was evaluated through PRCC method to find out the single most influential parameter and also combination of two most influential parameters was studied using SRCC method. The sensitivity of other remaining parameters was evaluated using Sobol's index. We then have framed and studied an optimal control problem considering the different medication involved in the Multi Drug Therapy (MDT) as control variables. We further studied this optimal control problem along with both MDT and steroid interventions. The finding from this novel and comprehensive study will help the clinicians and public health researchers involved in the process of elimination and eradication of leprosy.

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